When patients undergo removal (resection) and re-connection (anastomosis) of a segment or whole portion of the gastrointestinal tract, a significant number will develop anastomotic leaks despite being operated on by highly qualified surgeons in high-volume centers. Anastomotic leaks cause major long-term bowel dysfunction (incontinence), high cancer recurrence rates, decreased long term cancer survival, and sepsis-related deaths. The cause of anastomotic leaks remains unknown.
Cohn first proposed in 1955 that the microbial content of the gut plays a central role in the pathogenesis of anastomotic leak [4]. In his experiments, dogs were subjected to colon anastomosis and division of the mesenteric blood vessels to cause ischemia and delayed healing. One group was administered intraluminal antibiotics (tetracycline directly into the bowel via an indwelling catheter) and the other saline. Antibiotic treated dogs demonstrated complete anastomotic healing and recovery whereas those administered saline developed major leakage with peritonitis and death. Shardley was the first to suggest that P. aeruginosa might play a causative role in anastomotic leak [5], and performed the first randomized prospective placebo blinded trial with antibiotics confirming a role for microbes in human anastomotic leak [6]. Yet despite this and other similar compelling observations, a microbial mechanism for anastomotic leak is generally not accepted and, around the world, anastomotic leak is posited to be primarily a problem of poor technique and/or poor wound healing [7-9].
Accordingly, a need persists in the art for increased understanding of anastomotic leak, and for methods of preventing and treating diseases, disorders and conditions associated with anastomotic leak.